학술논문

Analysis of diagnostic test outcomes in a large loiasis cohort from an endemic region: Serological tests are often false negative in hyper-microfilaremic infections.
Document Type
Article
Source
PLoS Neglected Tropical Diseases. 3/14/2024, Vol. 18 Issue 3, p1-16. 16p.
Subject
*SERODIAGNOSIS
*DIAGNOSIS methods
*EXPLORATORY factor analysis
*ADVERSE health care events
*MEDICAL screening
*THEILERIA
Language
ISSN
1935-2727
Abstract
Background: The parasitic disease loiasis is associated with significant morbidity and mortality. Individuals with hyper-microfilaremia (greater than 20,000 microfilariae per mL of blood) may suffer from serious treatment-related or spontaneous adverse events. Diagnosing loiasis remains complex and primarily relies on direct parasite detection. In this study, we analyzed the performance of various diagnostic tests and the influence of parasitological and clinical factors on test outcomes in samples from individuals living in an endemic region. Methods: Data and samples were collected from rural Gabon. Loiasis was defined as either detectable microfilaremia, or a positive history of eyeworm as assessed by the RAPLOA questionnaire. Diagnostic testing included a quantitative PCR (qPCR) for detection of Loa loa DNA in blood samples, an in-house crude L. loa antigen IgG ELISA, and a rapid test for antibodies against the Ll-SXP-1 antigen (RDT). Sensitivity and specificity were determined for each test and factors potentially influencing outcomes were evaluated in an exploratory analysis. Results: ELISA, RDT and qPCR results were available for 99.8%, 78.5%, and 100% of the 1,232 participants, respectively. The ELISA and RDT had only modest diagnostic accuracy. qPCR was specific for L. loa microfilaremia and Cycle threshold values correlated with microfilarial density. Anti-L. loa IgG levels were highest in occult loiasis, and antibody levels correlated inversely with L. loa microfilarial density as did RDT line intensities. Only 84.6% and 16.7% of hyper-microfilaremic individuals tested positive by ELISA (11/13) and RDT (2/12), respectively. Conclusion: None of the tests demonstrated high sensitivity and specificity for loiasis. Indirect diagnostic assays were characterized by low specificity. Additionally, hyper-microfilaremic individuals often tested negative by RDT and ELISA, indicating that these tests are not suitable for individual case management in endemic populations. Author summary: Loiasis remains highly neglected despite recent evidence of significant loiasis-associated mortality and morbidity. This complex disease is difficult to diagnose, especially in endemic populations. Here, we assessed the performance of several diagnostic assays. In addition, an exploratory analysis of factors associated with the outcomes of indirect, serology-based tests was performed. The presented data show only moderate performance of indirect tests. Furthermore, amicrofilaremic loiasis was associated with higher quantitative serological test results. None of the indirect tests detected all cases of microfilaremic loiasis, including individuals with high and hyper-microfilaremia. As a negative test may not reliably exclude hyper-microfilaremic infections, these serological tests should not be used as screening tests in individual case management. This is important, as hyper-microfilaremic individuals are at increased risk of developing serious adverse events after treatment with drugs such as ivermectin or diethylcarbamazine. [ABSTRACT FROM AUTHOR]